Tirzepatide lowers HbA1c, body weight in adults with T2D

Treatment with tirzepatide once weekly results in significant decreases in glycated haemoglobin A1c (HbA1c) and body weight (BW), regardless of antiglutamic acid decarboxylase autoantibodies (GADA) status in adults with type 2 diabetes (T2D), according to a post hoc analysis of SURPASS.

These findings suggest the beneficial effects of tirzepatide on glycaemic control in latent autoimmune diabetes in adults (LADA).

Overall, 3,791 participants with confirmed GADA status were assessed, of whom 3,671 (96.8 percent) were GADA negative and 120 (3.2 percent) were GADA positive (76 with low and 44 with high GADA levels). Both groups had similar baseline characteristics, except for a slightly lower BMI in GADA-positive participants (mean BMI 32.2 vs 33.6 kg/m²). [J Clin Endoc Metab 2025;110:e962-e969]

Substantial reductions in HbA1c (‒2.11 percent vs ‒2.32 percent) and BW (‒9.2 vs ‒9.6 kg) were observed at week 40/42 in both groups (p<0.001 for both). Additionally, GADA-negative participants showed greater reductions in HbA1c (estimated difference 0.21 percent, 95 percent confidence interval [CI], 0.03‒0.39; p=0.024), but BW decrease did not differ significantly between groups (0.38 kg, 95 percent CI, ‒0.99 to 1.75; p=0.588).

“Weight reductions with tirzepatide treatment observed in GADA-positive individuals is clinically relevant given the recommendations of the American Diabetes Association/European Association for the Study of Diabetes consensus report and evidence supporting weight loss of 5 percent to 15 percent as a primary target in people diagnosed with T2D,” the researchers said. [Diabetes Care 2022;45:2753‐2786; Lancet 2022;399:358; Diabetes Care 2023;46(Suppl 1):S128‐S139]

β-cell function

The current findings also confirm the impairment of pancreatic β-cell function in LADA, as shown by lower homeostasis model assessment of β-cell function (HOMA2-B) in patients with LADA relative to those with T2D.

Treatment with tirzepatide resulted in a significant increase in β-cell function in GADA-positive individuals. In addition, fasting C-peptide levels remained stable in this population, indicating no sign of β-cell deterioration while on this medication.

“The increase in β-cell function observed with tirzepatide treatment in this study is consistent with previous observations,” according to the researchers. [Lancet Diabetes Endocrinol 2022;10:418‐429; J Clin Endocrinol Metab 2021;106:388‐396; J Endocr Soc 2023;7:bvad056; Peptides 2020;125:170213]

“[T]hese results suggest that increased β-cell function may contribute to the improved glycaemic control associated with tirzepatide in people with LADA,” they added.

Pooled data from SURPASS-2 to 5 was used in this post hoc analysis, which used mixed-model repeated measures from the efficacy analysis set. Adjustments were made for study and baseline covariates, such as age, sex, baseline values, BMI, and GADA status. Tirzepatide 5, 10, and 15 mg were used as intervention. The researchers then measured changes from baseline in HbA1c at weeks 40 (SURPASS-2, 3, and-5) and 42 (SURPASS-4) by GADA status.

“Future studies could help elucidate the long-term effect of the presence of GADA on the clinical progression of LADA and whether treatment with tirzepatide could delay or prevent insulin requirement in this population,” the researchers said. [Diabetes Care 2013;36:908‐913]